Orthotopic Cardiac Transplantation Research Articles

Multimodality Imaging in Advanced Heart Failure for Diagnosis, Management and Follow-Up: A Comprehensive Review.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), nuclear imaging and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. Nuclear imaging, CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. The aim is to highlight the novelty and unique aspects of recently published papers in the field. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Orthotopic Heart Transplantation Followed By Autologous Stem Cell Transplantation in Patients with Cardiac AL Amyloidosis: Results from a Single Centre Prospective Study

Background: Patients with advanced cardiac AL amyloidosis have a dismal prognosis, with an overall survival (OS) of only 5 months for Stage IIIb patients (Palladini et al, 2023). Induction chemotherapy followed by high dose chemotherapy and autologous stem cell transplantation (HDT and ASCT) has been widely used as treatment for AL amyloidosis. However, patients with advanced cardiac AL amyloidosis are often not suitable for HDT and ASCT due to high transplant related mortality (TRM). Orthotopic cardiac transplantation (OHT) following induction treatment may improve patient fitness and thus allow HDT and ASCT to deepen and prolong responses. We present our single centre, prospective study of patients with Stage IIIa and Stage IIIb cardiac AL amyloidosis who received OHT followed by sequential HDT and ASCT. Aims: The primary outcomes were 3 year OS and progression-free survival (PFS). Efficacy and safety were assessed as secondary outcomes. Efficacy was evaluated by light chain and cardiac response after ASCT. Safety was assessed by rate of TRM, cardiac rejection, opportunistic infections, and cytopenia related complications. Methods: During 2015 to 2021, patients with Stage IIIa or Stage IIIb AL amyloidosis aged under 65 years underwent OHT followed by HDT and ASCT. Patients with multiple myeloma were excluded. At approximately 6 months following OHT, patients underwent stem cell mobilization with granulocyte colony-stimulating factor alone followed by peripheral blood apheresis stem cell collection. Mycophenolate immunosuppression was temporarily withheld during stem cell mobilization and collection. Patients then received a high dose melphalan ASCT followed by 3-6 monthly assessments. Results: Nine patients (median age of 53 years, range 47-60 years) completed both OHT and ASCT. Seven other patients were screened but did not proceed with OHT. The cohort included both stage IIIa (55%) and stage IIIb (44%) patients. Most patients received cyclophosphamide-bortezomib-dexamethasone induction therapy (89%) and one patient received lenalidomide-bortezomib-dexamethasone. The median time from diagnosis of AL amyloidosis to OHT was 11 months (range 5-57 months) and median time from OHT to ASCT was 7 months (range 5-8 months). 3 year OS was 83% and PFS was 56% (Figure 1). At a median follow up of 37 months (range 17-69 months), 89% of patients remain alive. One patient with Stage IIIa disease who underwent HDT and ASCT with progressive disease (PD) died 28 months following ASCT due to PD. Subgroup analysis demonstrated 3 year OS in Stage IIIa patients of 75% compared to 100% in Stage IIIb (p=0.48). 3 year PFS was 53% in Stage IIIa patients and 66% in Stage IIIb (p=0.8). Patients in complete remission (CR) prior to ASCT had an improved 3 year OS of 100% compared to 66% for those in partial remission (PR) or with PD (p=0.32). 3 year PFS was significantly improved at 100% when ASCT occurred in CR compared to 0% in those in PR or with PD (p=0.01) (Figure 2). All patients either maintained a CR or achieved an improved haematological response following HDT and ASCT, with 89% of patients in CR at 6 months post ASCT. At the median follow up of 37 months, 78% were in CR and 22% had PD. At last follow up, there has been no documented amyloid recurrence in a cardiac allograft. There was no TRM noted in this study. All patients had cardiac rejection with 66% developing Grade 3A/2R rejection requiring methylprednisone. The most common infective complication was CMV reactivation (44%). Other infective complications included cryptococcal infection (11%), aspergillus and MAC infection (11%) and HSV reactivation requiring hospitalization (11%). During admission for HDT and ASCT, 89% had febrile neutropenia and there were no bleeding complications. Conclusions: We have demonstrated, in a prospective design, that sequential OHT/ASCT following induction therapy is safe in patients with Stage IIIa/b cardiac AL amyloidosis without an increase in TRM. This approach was associated with excellent survival outcomes compared with historical cohorts. Given the deep and prolonged responses seen with daratumumab based induction, a risk adapted strategy may be more appropriate moving forward, with only those not achieving a haematological CR undergoing consolidation ASCT following OHT.

Abstract 17764: Clinical Outcomes and Predictors of Vasoplegia in Patients Undergoing Orthotopic Cardiac Transplantation at a High-Volume Single-Center

Background: Patients undergoing heart transplantation are at significant risk of the developing post-operative vasoplegia, which is associated with poor outcomes. Despite significant burden to these patients, risk factors for development of vasoplegia are poorly understood. We assess these risk factors and outcomes in patients undergoing orthotopic heart transplant at our high-volume academic center. Methods: 173 patients underwent cardiac transplantation between January 1 st , 2015 and February 28 th 2022 at the Ohio State University Wexner Medical Center. Baseline demographics, operative characteristics, peri-operative management, and long-term follow-up data were obtained. Vasoplegia was defined as provider documentation of vasoplegia for patients with persistent hypotension requiring the use of one or more vasopressors to maintain mean arterial pressures >65 mmHg in the absence of other explainable causes (cardiogenic shock, sepsis, etc.) The two primary endpoints assessed were development of vasoplegia in the 48 hours post-transplant and all-cause mortality. Statistical significance was assessed using Chi-squared, analysis of variance, or Kruskal-Wallis where appropriate. Results: In total, 173 patients underwent cardiac transplantation. 89 (51.4%) developed vasoplegia in the post-operative period. 130 (75.1%) were males. The average age at transplant was 56 years. Patients with vasoplegia were more likely to have history of atrial fibrillation (p=0.01) and had higher BMI (p<0.01) compared to those without. There were otherwise no significant differences in demographic data such as past medical history and medication history in those with and without vasoplegia. Patients with vasoplegia had significantly higher cardiopulmonary bypass times (p=0.01), aortic cross-clamp times (p<0.01) and need for red blood cell transfusion peri-operatively (p=0.02). Patients with vasoplegia had higher 30-day mortality (p=0.03), however there was no significant difference in 1-year mortality for those with and without vasoplegia. Conclusions: Vasoplegia is common following orthotopic heart transplant, and short-term mortality is high. Appropriate risk-stratification is paramount in caring for these high-risk patients.

Stimulant Use for ADHD in a Cardiac Transplant Recipient: A Case Report

AbstractIntroductionMethylphenidate is a central nervous system stimulant used as first-line treatment for attention-deficit/hyperactivity disorder (ADHD). CNS stimulant use is associated with increased risk of cardiovascular events such as increased resting heart rate and blood pressure, sudden cardiac death, arrhythmia, and stroke. Its safety profile in recipients of cardiovascular transplants is unknown, and more research is warranted to determine the risk of adverse cardiac events due to stimulant medication in this population.MethodsClinical case report, n=1Results/Clinical CaseA 19-year-old female with a history of restrictive cardiomyopathy, cardiac arrest, and orthotopic cardiac transplant has been treated with methylphenidate for ADHD for approximately 2 years without incident. The patient was diagnosed with ADHD between the ages of 8 and 10 and historically was treated with stimulant medication. At age 13, she experienced a cardiac arrest after a volleyball game with 4–6 minutes of pulselessness. She was successfully resuscitated and underwent defibrillator placement. It was concluded that the patient had restrictive cardiomyopathy undetected at birth, leading to the need for orthotopic cardiac transplantation at age 16. After her cardiac arrest, the patient’s memory and cognition worsened, and approximately 1 year after her transplant, she was prescribed amantadine. The patient remained untreated for her ADHD until approximately 1.5 years after her cardiac transplant, at which time she underwent neuropsychological testing that showed findings consistent with attention deficit disorder, and was restarted on stimulant medication. Her transplant cardiologist and psychiatrist have collaborated in her ongoing treatment with methylphenidate 40 mg daily and monitoring symptom response and cardiac stability. Because the patient had previously been stable on stimulant medication for many years, it is reasonable to conclude that stimulant medication did not lead to her cardiac arrest. The patient reports that methylphenidate has been helpful in improving her functioning as a college student, through reduction of her ADHD symptoms. The patient’s blood pressure and heart rate remain within an acceptable range and she has not experienced any adverse cardiac events to date while taking methylphenidate.ConclusionThis case sheds light on the potential to treat cardiac transplant recipients with stimulant medication for ADHD. Although a careful evaluation of risk factors must be undertaken in cooperation with cardiology and other specialists, a role exists for the safe use of stimulant medications in the cardiac transplant population.FundingNo Funding

Pre-transplant immune cell function assay as a predictor of early cardiac allograft rejection.

ImmuKnow, an immune cell function assay that quantifies overall immune system activity can assist in post-transplant immunosuppression adjustment. However, the utility of pre-transplant ImmuKnow results representing a patient's baseline immune system activity is unknown. This study sought to assess if pre-transplant ImmuKnow results are predictive of rejection at the time of first biopsy in our cardiac transplant population. This is a single center, retrospective observational study of consecutive patients from January 1, 2018 to October 1, 2020 who underwent orthotopic cardiac transplantation at NYU Langone Health. Patients were excluded if a pre-transplant ImmuKnow assay was not performed. ImmuKnow results were categorized according to clinical interpretation ranges (low, moderate, and high activity), and patients were divided into two groups: a low activity group versus a combined moderate-high activity group. Pre-transplant clinical characteristics, induction immunosuppression use, early postoperative tacrolimus levels, and first endomyocardial biopsy results were collected for all patients. Rates of clinically significant early rejection (defined as rejection≥1R/1B) were compared between pre-transplant ImmuKnow groups. Of 110 patients who underwent cardiac transplant, 81 had pre-transplant ImmuKnow results. The low ImmuKnow activity group was comprised of 15 patients, and 66 patients were in the combined moderate-high group. Baseline characteristics were similar between groups. Early rejection occurred in 0 (0%) patients with low pre-transplant ImmuKnow levels. Among the moderate- high pre-transplant ImmuKnow group, 16 (24.2%) patients experienced early rejection (P=.033). The mean ImmuKnow level in the non-rejection group was the 364.9ng/ml of ATP compared to 499.3ng/ml of ATP for those with rejection (P=.020). Patients with low pre-transplant ImmuKnow levels had lower risk of early rejection when compared with patients with moderate or high levels. Our study suggests a possible utility in performing pre-transplant ImmuKnow to identify patients at-risk for early rejection who may benefit from intensified upfront immunosuppression as well as to recognize those where slower calcineurin inhibitor initiation may be appropriate.

Overcoming perioperative inflammation as a hurdle for successful preclinical orthotopic cardiac xenogeneic transplantations - particular in regard of the mandatory use of heart-lung machines.

After orthotopic cardiac xenotransplantation, the combination of both the inflammatory responses to the exposure of a recipient to the xenogeneic organ and the use of cardiopulmonary bypass has been assumed to cause detrimental side effects. These have been described not only to affect the transplanted organ (heart) itself, but also the recipient's lungs. In this article, we summarize how these possible detrimental processes can be minimized or even avoided. Data from eight pig-to-baboon orthotopic cardiac xenotransplantation experiments were analyzed with a special focus on early (within the first week) postoperative organ dysfunction and systemic inflammatory responses. Non-ischemic heart preservation and the careful management of the heart-lung machine were deemed essential to guarantee not only the immediate function of the transplanted xenogeneic organ but also the prompt recovery of the recipient. After weaning from cardiopulmonary bypass, very low catecholamine amounts were needed to ensure an adequate pump function and cardiac output. Central venous oxygen saturation and serum lactate levels remained within normal ranges. All animals were successfully weaned from ventilation within the first postoperative hours. Serum parameters of the transplants and native kidneys and livers were initially slightly elevated or always normal, as were hemoglobin, LDH, and platelet measurements. Markers of systemic inflammation, C-reactive protein, and IL-6 were slightly elevated, but the reactions caused no lasting damage. Consistent short-term and long-term results were achieved after orthotopic cardiac pig-to-baboon transplantation without detrimental inflammatory responses or signs of multiorgan failure. In comparison to allogeneic procedures, non-ischemic heart preservation was important for successful immediate organ function, as was the management of the heart-lung machine. Thus, we believe that genetically modified porcine hearts are ready for use in the clinical setting.

Effects of Ischemic Time on Survival After Cardiac Transplantation in a Contemporary Cohort

Purpose Limited availability of cardiac allografts and the risk of recipient waitlist mortality incentivizes expansion of the donor pool outside of the recommended maximum four hour ischemic time. We aimed to investigate whether prolonged donor ischemic time is associated with all-cause mortality after heart transplant in a modern cohort. Methods Data from initial isolated orthotopic cardiac transplantations performed on adult recipients from 2010 and 2017 reported to the United Network for Organ Sharing (UNOS) registry were analyzed. Patient survival rates at 1, 3, and 5 years were estimated using Kaplan-Meier with log-rank test. Subjects were stratified into four groups based on ischemic time: <3 hours (2.2 ± 0.55 hours, 21.1%) 3-4.5 hours (3.69 ± 0.42, 24.4%), 4.5-6 hours (5.16 ± 0.43, 10.5%), and >6 hours (7.44 ± 1.66, 6.2%). Results The median ischemic time was 3.55 (2.68, 4.63) hours. Prolonged ischemic time was associated with worse outcomes at 1 year (P<0.001), 3 years (P<0.001), and 5 years (P<0.001) in Kaplan-Meier analyses. Comparison to historical data suggests that advances in management have been unable to attenuate the hazard associated with longer ischemic times. Conclusion While concerns over ischemic time duration have persisted since the 1970s when institutions began exploring long-distance organ procurement as a means of expanding the donor pool, these data are among the first to show that extended ischemic times are significantly associated with short- and long-term all-cause mortality in a contemporary cohort. Anticipated ischemic time must be considered when assessing a potential donor. Further research is warranted to determine precise guidelines. Limited availability of cardiac allografts and the risk of recipient waitlist mortality incentivizes expansion of the donor pool outside of the recommended maximum four hour ischemic time. We aimed to investigate whether prolonged donor ischemic time is associated with all-cause mortality after heart transplant in a modern cohort. Data from initial isolated orthotopic cardiac transplantations performed on adult recipients from 2010 and 2017 reported to the United Network for Organ Sharing (UNOS) registry were analyzed. Patient survival rates at 1, 3, and 5 years were estimated using Kaplan-Meier with log-rank test. Subjects were stratified into four groups based on ischemic time: <3 hours (2.2 ± 0.55 hours, 21.1%) 3-4.5 hours (3.69 ± 0.42, 24.4%), 4.5-6 hours (5.16 ± 0.43, 10.5%), and >6 hours (7.44 ± 1.66, 6.2%). The median ischemic time was 3.55 (2.68, 4.63) hours. Prolonged ischemic time was associated with worse outcomes at 1 year (P<0.001), 3 years (P<0.001), and 5 years (P<0.001) in Kaplan-Meier analyses. Comparison to historical data suggests that advances in management have been unable to attenuate the hazard associated with longer ischemic times. While concerns over ischemic time duration have persisted since the 1970s when institutions began exploring long-distance organ procurement as a means of expanding the donor pool, these data are among the first to show that extended ischemic times are significantly associated with short- and long-term all-cause mortality in a contemporary cohort. Anticipated ischemic time must be considered when assessing a potential donor. Further research is warranted to determine precise guidelines.

Role of chronic continuous intravenous lidocaine in the clinical management of patients with malignant type 3 long QT syndrome.

Type 3 long QT syndrome (LQT3) is caused by pathogenic, gain-of-function variants in SCN5A leading to a prolonged action potential, ventricular ectopy, and torsades de pointes. Treatment options include pharmacotherapy, cardiac denervation, and/or device therapy. Rarely, patients with malignant LQT3 require cardiac transplantation. The purpose of this study was to evaluate the role of chronic continuous intravenous (IV) lidocaine as a therapeutic option for select patients with LQT3 refractory to standard therapy. We performed a retrospective review of patients evaluated and treated at Mayo Clinic and identified 4 of 161 patients with LQT3 (2.5%) who were refractory to standard therapies and therefore treated with IV lidocaine. There were 4 patients (2 female [50%]). The median age at first IV lidocaine infusion was 2 months (interquartile range 1.5-4.8 months), and the median cumulative duration on IV lidocaine was 11.5 months (interquartile range 8.7-17.8 months). The main indication for IV lidocaine in all patients was persistent ventricular arrhythmias. Before IV lidocaine, all patients received an implantable cardioverter-defibrillator, and while on intermittent IV lidocaine, all patients underwent bilateral cardiac sympathetic denervation. Additionally, 2 (50%) patients had cardiac ablation for premature ventricular complexes. In all patients, lidocaine infusion resulted in a significant reduction of LQT3-triggered cardiac events. The main side effects of IV lidocaine observed were dizziness (n= 2, 50%) and seizures (n = 2, 50%). During follow-up, 3 of 4 (75%) patients underwent orthotopic cardiac transplantation. The remaining patient continues to receive IV lidocaine bolus for rescue as needed. For patients with LQT3 who are refractory to standard treatment, chronic IV lidocaine infusion can be used as a potential "bridge to transplant."

Procainamide pharmacokinetics during extracorporeal membrane oxygenation.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Surgical management of divided atrial chambers.

The morphological variations when one, or both, of the atrial chambers is subdivided, are many and varied. We sought to address clinical presentations, potentially misdiagnosed cases, diagnostic modalities, surgical approaches, and outcomes of this "family" of uncommon lesions. A total of 193 published investigations were synthesized. Diagnostic information was provided by clinical presentation, and multimodality imaging studies. Almost three-quarters of patients with divided atrial chambers present during infancy with severe pulmonary hypertension and cardiac failure. Associated cardiac and extra-cardiac defects are present in between half and nine-tenths of cases. Acquired division of the left atrium has been reported after the Fontan operation, orthotopic cardiac transplantation, and complicated aortic valvar infective endocarditis. Surgery under cardiopulmonary bypass remains the definitive treatment. Balloon dilation may be considered in anatomically compatible variants in the setting of cardiac failure and pregnancy as a bridge todefinitive treatment. Overall, mortality has been cited between nil to 29%. Presentation during infancy, associated congenital anomalies, pulmonary hypertension, and surgery in the previous era, have been the reported causes of death. The operative survivors have long-term favourable outcomes, with near normal cardiac dimensions and low risk of recurrence. While asymptomatic patients with division of the right atrium do not need treatment, surgical resection of the dividing partition under cardiopulmonary bypass is recommended in symptomatic patients with complex anatomy, the spinnaker malformation, or associated cardiac anomalies. Balloon dilation may be considered in uncomplicated patients with less obstructive lesions. Hybrid intervention and endoscopic robotic correction also have been performed. Resection of the dividing shelf allows the survivors to regain near normal dimensions with a low risk of recurrence. We submit that an increased appreciation of the anatomic background to division of the atrial chambers will contribute to improved surgical management.

Expanding Spectrum of Desmin-Related Myopathy, Long-term Follow-up, and Cardiac Transplantation.

We aimed to determine the genetic and clinical phenotypes of patients with desmin-related myopathy and long-term outcomes after cardiac transplantation. We performed a retrospective review of cardiac and neurologic manifestations of patients with genetically confirmed desmin-related myopathy (January 1, 1999-January 1, 2020). Twenty-five patients in 20 different families were recognized. Median age at onset of symptoms was 20 (range 4-50) years; median follow-up time was 36 (range 1-156) months. Twelve patients initially presented with skeletal muscle involvement, and 13 presented with cardiac disease. Sixteen patients had both cardiac and skeletal muscle involvement. Clinically muscle weakness distribution was distal (n = 11), proximal (n = 4), or both (n = 7) in 22 patients. Skeletal muscle biopsy from patients with missense and splice site variants (n = 12) showed abnormal fibers containing amorphous material in Gomori trichrome-stained sections. Patients with cardiac involvement had atrioventricular conduction abnormalities or cardiomyopathy. The most common ECG abnormality was complete atrioventricular block in 11 patients, all of whom required a permanent pacemaker at a median age of 25 (range 16-48) years. Sudden cardiac death resulting in implantable cardioverter-defibrillator (ICD) shocks or resuscitation was reported in 3 patients; a total of 5 patients had ICDs. Orthotopic cardiac transplantation was performed in 3 patients at 20, 35, and 39 years of age. Pathogenic variants in desmin can lead to varied neurologic and cardiac phenotypes beginning at a young age. Two-thirds of the patients have both neurologic and cardiac symptoms, usually starting in the third decade. Heart transplantation was tolerated with improved cardiac function and quality of life.

The Genetically Engineered Heart as a Bridge to Allotransplantation in Infants Just Around the Corner?

BackgroundMortality for infants on the heart transplant waitlist remains unacceptably high, and available mechanical circulatory support is suboptimal. Our goal is to demonstrate the feasibility of utilizing genetically engineered pig (GEP) heart as a bridge to allotransplantation by transplantation of a GEP heart in a baboon. MethodsFour baboons underwent orthotopic cardiac transplantation from GEP donors. All donor pigs had galactosyl-1,3-galactose knocked out. Two donor pigs had human complement regulatory CD55 transgene and the other 2 had human complement regulatory CD46 and thrombomodulin. Induction immunosuppression included thymoglobulin, and anti-CD20. Maintenance immunosuppression was rapamycin, anti-CD-40, and methylprednisolone. One donor heart was preserved with University of Wisconsin solution and the other three with del Nido solution. ResultsAll baboons weaned from cardiopulmonary bypass. B217 received a donor heart preserved with University of Wisconsin solution. Ventricular arrhythmias and depressed cardiac function resulted in early death. All recipients of del Nido preserved hearts easily weaned from cardiopulmonary bypass with minimal inotropic support. B15416 and B1917 survived for 90 days and 241 days, respectively. Histopathology in B15416 revealed no significant myocardial rejection but cellular infiltrate around Purkinje fibers. Histopathology in B1917 was consistent with severe rejection. B37367 had uneventful transplant but developed significant respiratory distress with cardiac arrest. ConclusionsSurvival of B15416 and B1917 demonstrates the feasibility of pursuing additional research to document the ability to bridge an infant to cardiac allotransplant with a GEP heart.

Multiple Bridging: Recovery, Decision, Transplantation, Recovery

Introduction This case describes multiple forms of short term mechanical circulatory support (sMCS) used sequentially in the same patient, and illustrates the role of different clinical goals of sMCS. Case Report A 59 year old man with previous coronary artery bypass surgery attended with troponin positive acute coronary syndrome. After workup, he went for PCI to a native coronary chronic total occlusion using anterograde/retrograde wires. Unfortunately, the left internal mammary graft was dissected, and he suffered cardiac arrest. Day 0: Impella CP as bridge to recover y : During resuscitation an Impella CP was placed via his right femoral artery and resolved circulatory arrest. Further PCI was performed to the LIMA ostium with restoration of flow. He was transferred to ITU. Day 3: Peripheral VA-ECMO as bridge to decision: His clinical status improved, but he remained in shock. His support was upgraded to peripheral veno-arterial (VA) extra-corporeal membrane oxygenation (ECMO), leaving the Impella in place as an LV vent. Day 14: BIVAD as bridge to transplantation: He remained MCS-dependent, and had no absolute contraindications to advanced therapies. He went to theatre for implantation of bilateral short term ventricular assist devices (BI-VAD) to optimise his organ support prior to transplantation. He was placed on the super-urgent waiting list. He had intermittent ventricular fibrillation but continued to mobilise on the ITU. Day 48: Transplantation and bridge to recovery with central ECMO: After 34 days on BIVAD, he underwent orthotopic cardiac transplantation. Due to vasoplegia and RV dysfunction, he was weaned from cardiopulmonary bypass onto central ECMO. Day 50: Weaning support - percutaneous RVAD as bridge to recover y : There was persistent RV dysfunction. Central ECMO was exchanged for a Protek RVAD. Day 56: Explant of RVAD: His status continued to improve. The RVAD was weaned and explanted after 6 days. Day 73: Discharge home: He required intense physiotherapy. After 73 days in hospital he was discharged home. At the time of submission he is alive at 291 days post transplant. Summary This man's successful outcome was facilitated by judicious use of sMCS, on each occasion with a clear strategy in mind. Surgically implanted and percutaneous modes were used. Collaboration between cardiologists, intensivists and cardiac surgeons was essential to facilitate optimal care.

Valvular surgery in donor hearts before orthotopic heart transplantation

Donor heart shortage has extended the waiting time and increased the mortality of patients on the transplant waiting list. Widening old standard donor criteria has successfully increased the number of heart transplantations, but for many years, a valve disease in a donor heart has been considered a primary contraindication for organ donation. To analyse the results of aortic and mitral valvular surgery in marginal donor hearts with valvulopathy before orthotopic heart transplantation. Between January 2012 and November 2015, we performed 53 heart transplantations in our department. In four donors, echocardiography performed at the time of organ procurement showed a valvular disease: three had moderate-to-severe mitral regurgitation; and one had moderately severe aortic valve stenosis. The mean bench mitral repair and aortic replacement time, aortic cross-clamp time and total ischaemic time were: 18 (range 7-25) minutes, 78.7 (range 57-98) minutes and 184 (range 89-255) minutes, respectively. Intraoperative transoesophageal echocardiography showed good mitral repair or aortic prosthetic valve function, and good right and left ventricular function. One patient died of infectious pneumonia after 1 month. The mean duration of follow-up for the patients discharged home was 75±13 months, and all have returned to an active unrestricted lifestyle. Our limited series demonstrates that conventional valvular procedures performed on otherwise healthy donor hearts with mitral and aortic valve pathology can efficaciously expand the donor pool for orthotopic cardiac transplantation and decrease the mortality rate on the waiting list.

Transition to Advanced Therapies in Elderly Patients Supported by Extracorporeal Membrane Oxygenation Therapy

Although the use of extracorporeal membrane oxygenation (ECMO) continues to increase, very little is known about how age influences the transition to definitive advanced therapies. Using the National Inpatient Sample database from 2008 to 2017, we analyzed patients supported by ECMO for cardiogenic shock and separated patients into 2 age cohorts: < 65 years and ≥ 65 years. Primary outcomes of interest included the proportion of patients undergoing orthotopic cardiac transplantation (OHT) and left ventricular assist device (LVAD) implantation. Over the study period, we identified 16,132 hospitalizations of people with cardiogenic shock requiring ECMO support. Significantly fewer patients in the older group underwent OHT compared to the younger group (0.4% vs 1.2%, P < 0.001). Compared to the younger group, a lower proportion of those ≥ 65 years received an LVAD (3.7% vs 5.8%, P < 0.001). LVAD implantation increased over the study period in both age cohorts, whereas OHT increased only in the < 65 group (P < 0.05, all). After multivariable adjustment, patients in the oldest age group were still less likely to receive an LVAD (odds ratio 0.54; confidence interval: 0.43-0.69, P < 0.001) and continued to have the highest odds of in-hospital mortality (odds ratio 1.53; confidence interval : 1.39-1.69, P < 0.001). Survival of patients ≥ 65 years requiring ECMO for cardiogenic shock is poor and less commonly includes transition to definitive advanced therapies. Although we must stress that no patient should be denied ECMO based solely on age, we believe our results may be helpful for providers when counseling patients and their families.

Peripheral T cell lymphoma, NOS with aberrant αβ and γδ T cell receptor expression in a post-heart transplant patient

Three main patterns of T cell receptor (TCR) expression are identified in peripheral T cell lymphoma (PTCL): TCR-αβ type, TCR-γδ type, and TCR silent type. Cases of PTCL that express both αβ and γδ receptors are rare. Here, we report a case of PTCL-NOS (not otherwise specified) with dual αβ and γδ expression in a 61-year-old female 6 years after orthotopic cardiac transplant. The patient presented with fatigue, fever, worsening anemia, and thrombocytopenia. A chest CT showed multiple irregular lung nodules and diffuse lymphadenopathy. Cytology evaluation of the lymph nodes revealed large atypical lymphocytes with immunopositivity for CD3, CD8, CD56, TIA1, and granzyme B and immunonegativity for CD5 and CD30. Epstein-Barr virus (EBV) was not detected by EBV-encoded RNA (EBER) in situ hybridization study. The corresponding flow cytometry demonstrated abnormal T cells with TCR-αβ and TCR-γδ expression and loss of CD5 expression. A TCR gene rearrangement study demonstrated the presence of a clonal lymphoid population with TCRβ and TCRγ rearrangements. The patient was deceased within 2 months despite aggressive treatment. The findings were consistent with an EBV-negative, monomorphic T cell post-transplant lymphoproliferative disorder (PTLD) with features of PTCL-NOS. A literature review of T cell lymphoma with co-expression of TCR-αβ and TCR-γδ was performed. A case of aggressive PTCL with dual expression of TCR-αβ and TCR-γδ in a post-transplant setting has not been previously reported.

The Role of Biventricular Implantable Defibrillator in Heart Transplant Recipients

Background Sudden cardiac death and heart failure are common complications following orthotopic heart transplantation. The role of biventricular implantable cardioverter-defibrillators (BiV ICDs) in this population is unknown with minimal available data. Objective Highlight the safety and utility of BiV ICD placement among orthotopic heart transplant recipients. Case A 69-year-old male with a medical history notable for type II diabetes, and prior non-ischemic cardiomyopathy requiring BiV ICD and after that, he needed left ventricular assist device (LVAD) placement and ultimately heart transplantation and explantation of his prior BiV ICD. He developed ischemic cardiomyopathy. Cardiac MRI revealed left ventricular dilation, thinning and dyskinesis in the distribution of the left anterior descending (LAD coronary artery and a reduced ejection fraction of 25%. Cardiac catheterization demonstrated 100% occlusion of the middle left anterior descending coronary artery with distal collateralization. ECG demonstrated RBBB with QRS duration of 157 milliseconds. We proceeded with new BiV ICD on the right side due to vein occlusion on the left side. On 24-month follow up, the patient is doing well with no heart failure admission and no ICD therapy. Conclusions BiV ICD placement might be a safe and viable option among orthotopic cardiac transplant recipients to manage heart failure and prevent sudden cardiac death.

Heart transplantation in a patient with primary malignant tumor

The article looks at a clinical case of a 31-year-old female with signs of paroxysmal ventricular tachycardia and Morgagni–Adams–Stokes syndrome. In April 2014, electrophysiological examination revealed a source of ventricular tachycardia localized in the apices of the right and left ventricles of the patient. The sources were then subjected to RF ablation followed by cardioverter-defibrillator implantation. Subsequent antiarrhythmic therapy failed to improve her state. In September 2016 the patient was re-examined and underwent RF ablation of the apical region of the right ventricle. Later on, taking into account continuously recurrent life-threatening cardiac rhythm disorders, as well as unpromising strategies for further conservative treatment, she was put on the waiting list and then underwent orthotopic cardiac transplantation. Histological examination and immunohistochemistry assay showed leiomyosarcoma in the source of ventricular tachycardia previously found in the apex of the right ventricle. This clinical case demonstrates a diversity of clinical manifestations of primary malignant tumors of the heart that pose a challenge for intravital diagnostics and interpretation of a clinical picture.

Mechanical bridge to heart transplantation

Purpose of the study. The purpose of the work is to assess the effectiveness of using mechanical support for blood circulation in potential cardiac recipients who need urgent transplantation.&#x0D; Material and methods. The study included 47 patients and divided into two groups. The first group included 8 potential cardiac recipients, who had established mechanical support for the BiVAD blood flow. The second group included 39 potential cardiac recipients, who had LVAD's mechanical support for the circulatory system. The main disease that led to the development of terminal congestive heart failure was dilated cardiomyopathy. The INTERMACS scale was used to assess the patient's status. A Scale for the Classification of Patients with Progressive Heart Failure. We used the UNOS scale to assess the status of the patient who needed orthotopic cardiac transplantation. The algorithm of the Thoracic Committee of a single size distribution of organs for determining the urgent implementation of cardiac transplantation.&#x0D; Results and discussion. Biventricular support is necessary for patients with high central venous pressure, increased pulmonary vascular resistance or with malignant arrhythmias, resistant to drug therapy. For the purpose of the final therapy and biventricular support, the system of choice can be a fully artificial heart.&#x0D; Conclusions. Indications for biventricular circulation support are pronounced hemodynamic manifestations of impaired pumping function of the right and left ventricles of the transplanted heart. Systems DK (VAD) is the most effective «bridge to transplantation». It is important to choose the device for the patient, not the patient for the device.

The ST2 diagnostic value in selection of patients for heart transplantation and post-transplant period

Purpose of the study. Study ST2 diagnostic marker in the development and severity of heart failure, evaluation of transplant status and the risk of developing a rejection crisis, as well as the risk of death in patients with cardiovascular disease.&#x0D; Material and methods. There were 41 patients under observation. The cases were conventionally divided into two groups: the first group of patients with chronic heart failure (n = 28), and the control group who performed orthotopic transplantation of the heart (n = 13).&#x0D; Results and discussion. These results suggest that ST2 is a real marker of chronic heart failure or a good predictor of mortality in decompensated patients. Changes in ST2 levels in patients after orthotopic cardiac transplantation may be potentially useful in detecting acute cellular rejection, as well as in controlling rejection therapy. The article is devoted to the analysis of the prognostic role of the ST2 biomarker in the pre and post-transplantation period. ST2 is one of the most promising diagnostic markers for the development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes in response to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. It is likely that ST2 level measurement of heart transplantation mayhave a diagnostic and prognostic value when evaluating the graft state and the risk of developing rejection.&#x0D; Conclusions. ST2 is one of the most promising diagnostic markers of development and severity of heart failure, as well as the risk of death in patients with cardiovascular disease. ST2 is expressed in cardiomyocytes inresponse to pathological processes and various mechanical damage in the heart, which allows to diagnose cardiovascular diseases even before clinical manifestations. Measuring the level of ST2 for heart transplantation may have a diagnostic and prognostic value in evaluating the condition of the graft and the risk of developing rejection.